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How Can We Determine the Role of Radiotherapy in the Treatment of Localized Aggressive Non-Hodgkin's Lymphoma?

Dr Lutfi Kirdar Kartal Education and Research Hospital, Istanbul, Turkey

To the Editor:

In the recently published phase III trial by Groupe d'Etude des Lymphomes de l'Adulte (GELA)—a group of authors who are opponents of adjuvant radiotherapy in treatment of aggressive localized non-Hodgkin's lymphoma—the role of radiotherapy was questioned again.^1,2 However, we believe that there are certain drawbacks in their trial. First, primary failures are two times more common in the group assigned to adjuvant radiotherapy (6% v 3%), although the two groups were treated with the same chemotherapy regimen (four cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone [CHOP]). Secondly, more than 10% of the patients allocated to adjuvant radiotherapy did not receive it, and in one fourth of patients, this was attributed to poor response obtained with CHOP chemotherapy. Thus, the two groups, although they appear to be well-balanced with respect to stage, age-adjusted international prognostic index scores, and other factors such as bulky disease, do not seem similar with respect to treatment sensitivity. Another drawback of the study that may have affected the results was the administration of radiotherapy to the majority of the partial responders in the CHOP alone arm (six of eight patients). Despite all of these factors negatively influencing the results of CHOP plus radiotherapy, the total number of relapsed patients in this group was lower than the total number of relapsed patients treated only with chemotherapy (66 v 79 patients). More interestingly, although not mentioned in the study, radiotherapy achieved its objective, as the infield failure rates decreased more than half by radiotherapy when compared with the group receiving only chemotherapy (21% v 47%).

Fewer lymphoma relapses (66 v 79 patients) despite higher lymphoma-related deaths (70 v 65 patients) in the CHOP plus radiotherapy arm seems paradoxical, and the authors claim that the administration of radiotherapy alters the pattern of localization of relapses, but does not decrease the overall rate. In their reply³ to correspondences concerning the GELA's former trial, they state that the aim of first-line treatment of localized lymphoma is to improve survival rather than to control local disease. But how can we talk about cure without controlling malignancy locally? In contrast to many other malignant diseases, negative effect of local recurrence on survival in lymphomas may be offset by the efficacy of salvage treatments. But still the adverse effect of bulky disease on survival has been demonstrated in a multivariate analysis.²

Another important point that must be mentioned, which was also observed in this study, was the different sensitivity and outcome of aggressive non-Hodgkin's lymphomas to the same treatment. This difference may depend on many and even unknown factors such as WHO classification, site of origin of lymphoma, and pattern of gene and protein expression, which may be different even in the same lymphoma type.⁴

In order to prove the benefit of radiotherapy in localized aggressive non-Hodgkin's lymphomas, it would be better to stage patients with positron emission tomography scanning rather than with conventional imaging, and to include patients only with a single WHO-classified disease entity with same localization, size, and International prognostic index scores. In this way the groups can be made more homogenous with respect to treatment sensitivity.

AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

The author(s) indicated no potential conflicts of interest.

REFERENCES

1. Bonnet C, Fillet G, Mounier N, et al: CHOP alone compared with CHOP plus radiotherapy for localized aggressive lymphoma in elderly patients: A study by the Groupe d'Etude des Lymphomes de l'Adulte. J Clin Oncol 25:3958-3964, 2007[Abstract/Free Full Text]

2. Reyes F, Lepage E, Ganem G, et al: ACVBP versus CHOP plus radiotherapy for localized aggressive lymphoma. N Engl J Med 352:1197-1205, 2005[Abstract/Free Full Text]

3. Hoecht S, Hinkelbein W: Treatment of localized lymphoma. N Engl J Med 352:2449-2451, 2005[Free Full Text]

4. Armitage JO: Defining the stages of aggressive non-Hodgkin's lymphoma - a work in progress. N Engl J Med 352:1250-1252, 2005[Free Full Text]

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This Article Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Gemici, C. Articles by Salepci, T. Search for Related Content PubMed PubMed Citation Articles by Gemici, C. Articles by Salepci, T. Social Bookmarking                            What's this?